Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
What are examples of chronic problems?
Common chronic conditions are arthritis, Alzheimer's disease, diabetes, heart disease, high blood pressure, and chronic kidney disease. Unlike acute conditions, chronic health conditions cannot be cured—only controlled.Mar 9, 2020
plexrec
https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.12013
A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer's disease therapy: Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study
Harald Hampel, Coralie Williams, Adrien Etcheto, Federico Goodsaid, Frédéric Parmentier, Jean Sallantin, Walter E. Kaufmann, Christopher U. Missling, Mohammad Afshar
First published: 19 April 2020 https://doi.org/10.1002/trc2.12013Citations: 13
Abstract
Introduction
The search for drugs to treat Alzheimer's disease (AD) has failed to yield effective therapies. Here we report the first genome-wide search for biomarkers associated with therapeutic response in AD. Blarcamesine (ANAVEX2-73), a selective sigma-1 receptor (SIGMAR1) agonist, was studied in a 57-week Phase 2a trial (NCT02244541). The study was extended for a further 208 weeks (NCT02756858) after meeting its primary safety endpoint.
Methods
Safety, clinical features, pharmacokinetic, and efficacy, measured by changes in the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), were recorded. Whole exome and transcriptome sequences were obtained for 21 patients. The relationship between all available patient data and efficacy outcome measures was analyzed with unsupervised formal concept analysis (FCA), integrated in the Knowledge Extraction and Management (KEM) environment.
Results
Biomarkers with a significant impact on clinical outcomes were identified at week 57: mean plasma concentration of blarcamesine (slope MMSE:P < .041), genomic variants SIGMAR1 p.Gln2Pro (?MMSE:P < .039; ?ADCS-ADL:P < .063) and COMT p.Leu146fs (?MMSE:P < .039; ?ADCS-ADL:P < .063), and baseline MMSE score (slope MMSE:P < .015). Their combined impact on drug response was confirmed at week 148 with linear mixed effect models.
Discussion
Confirmatory Phase 2b/3 clinical studies of these patient selection markers are ongoing. This FCA/KEM analysis is a template for the identification of patient selection markers in early therapeutic development for neurologic disorders.
Abstract
Introduction
The search for drugs to treat Alzheimer's disease (AD) has failed to yield effective therapies. Here we report the first genome-wide search for biomarkers associated with therapeutic response in AD. Blarcamesine (ANAVEX2-73), a selective sigma-1 receptor (SIGMAR1) agonist, was studied in a 57-week Phase 2a trial (NCT02244541). The study was extended for a further 208 weeks (NCT02756858) after meeting its primary safety endpoint.
Methods
Safety, clinical features, pharmacokinetic, and efficacy, measured by changes in the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), were recorded. Whole exome and transcriptome sequences were obtained for 21 patients. The relationship between all available patient data and efficacy outcome measures was analyzed with unsupervised formal concept analysis (FCA), integrated in the Knowledge Extraction and Management (KEM) environment.
Results
Biomarkers with a significant impact on clinical outcomes were identified at week 57: mean plasma concentration of blarcamesine (slope MMSE:P < .041), genomic variants SIGMAR1 p.Gln2Pro (?MMSE:P < .039; ?ADCS-ADL:P < .063) and COMT p.Leu146fs (?MMSE:P < .039; ?ADCS-ADL:P < .063), and baseline MMSE score (slope MMSE:P < .015). Their combined impact on drug response was confirmed at week 148 with linear mixed effect models.
Does this meet PEER Reviewed Paper criteria? Looks like it does. Dr.M.is one of credited people contributors. First Published 16 June 2023 (last Friday) .
https://doi.org/10.1002/alz.059024
WHAT COLOR IS THIS RED PIECE OF PAPER???[color=red][/color]
[color=red][/color]
[img][/img]
Jimmy_Mcy...looks like they got some dates crossed...note 2023...???
Has FDA painted itself into a corner on the Amyloid thesis? If the AVXL alternative shows evidence of no risk and efficacy using a daily pill then the hill is even steeper for Amyloid , unless BP shows strong evidence of efficacy (for which no evidence exists) . If you were calling the shots at FDA...become a hero and take no risks w/new treatment or......??....it seems like a no brainer(not intended as humor).
Folks at FDA must be getting tired by now. They are in the spotlight and they know it.
a reasonable comparison of results shows?....WGT
AVXL:
Conclusions
This analysis identified a gene network that is differentially expressed in patients treated with blarcamesine after 14 weeks of treatment, compared to placebo. The biological relevance of this gene network was assessed. Pathway analysis confirmed the impact of the treatment on pathways involved in neurodegenerative diseases The identification of a gene network as the blarcamesine response pathway lays the foundation to better understand the mechanism of action at the molecular level of blarcamesine, thus unlocking characterization of responders based on molecular profiling, as well as identification of new indications in the area of neurodegenerative and other disorders.
Suggest you re-read...https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.059024
It establishes what steps, methods and process sequence are used to do the work and to measure the results.
Definitions 21 CFR 820.3 (z)(1) Process Validation means establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications.Sep 30, 2015
Quality System Regulation Process Validation - FDA
This language reads as a V&V (verification and Validation) statement written in FDA speak. In other words, it may be read as a statement of "Validation" for the methods used. Very positive.
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.059024
This language reads as a V&V (verification and Validation) statement written in FDA speak. In other words, it may be read as a statement of "Validation" for the methods used. Very positive.
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.059024
hnnbadger
s this considered a “peer reviewed “article ?
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.059024
Coming from the Alzheimer’s Association is a big step forward IMO!
Redshoulder.
MOA study from the Alzheimer Association. New Article, Date June 16th"
Very powerful words here --take note shorties !!!---While the data already released was superior to lecanemab, once the 50 mg alone cohort data comes out the results should be considerably better than for the combined group. So I think the data so far was encouraging, but the best news is yet to come — and the stock remains a favorite for 2023.
plexrec
Very, very positive - smoke free assessment ...happy to see a clear message.
[quoteAnavex (AVXL), is a biopharmaceutical company dedicated to the development of novel drug candidates to treat central nervous system diseases with very encouraging results so far in Alzheimer’s, Parkinson’s and Rett Syndrome, suggests Tom Bishop, editor of BI Research.
The big news for Anavex was the release of the preliminary data from the 508 patient, placebo controlled, double-blind, 48-week, Phase 2b/3 ANAVEX 2-73 (blarcamesine or A2-73) Alzheimer’s trial which tested 3 equal cohorts with placebo, 30 mg or 50 mg oral doses.
First I need to point out two very important things:
1) There was a delay in getting the data from one of the trial sites that resulted in the company only getting the data from the third party statistical analysis company just 1 day before it was on the schedule to present at the CTAD Alzheimer’s conference. This therefore limited what the company could accurately report at that time.
2) Some of the best results from an earlier trial were for the 50 mg. cohort, while the 30 mg barely worked. However, ALL of the analysis presented recently was for the combined 30+50 mg patients as a single cohort, diluting the efficacy results.
Therefore, results yet to come should be even better once the company reports on the 50 mg cohort by itself. The primary endpoints were the reduction in the decline of cognition (ADAS-COG) and activities of daily living (ADCS-ADL) at 48 weeks.
On this the company said, “The Anavex 2-73 (blarcamesine) study met the primary and key secondary endpoints showing statistically significant reduction of clinical decline in global cognitive and functional scales in a clinical study of patients with early Alzheimer’s disease.” (MMSE baseline scores 20-28).
And more to the point: “Treatment with ANAVEX®2-73 statistically significantly reduced cognitive decline, measured with ADAS-Cog, compared to placebo at end of treatment by 45% (p=0.033).”
This is the most significant and directly on point outcome released so far for this trial given this was considerably better than Biogen/Eisai’s 27% slowing of cognitive decline recently reported for lecanemab.
Nonetheless lecanemab's meager result caused those two companies to increase $20 billion in market cap overnight. Most observers believe this Phase 3 result paves the way for likely FDA approval. However, Anavex’s drug beat lecanemab by a wide margin (a 45% slowing vs. 27%) in its Phase2b/3 trial.
But here’s the thing … Biogen’s drug requires IV infusion therapy and periodic MRIs to check for brain swelling and bleeding (two nasty side effects of lecanemab), while A2-73 is a pill and doesn’t require periodic MRI’s, a huge advantage even ignoring that A2-73 worked better.
While the data already released was superior to lecanemab, once the 50 mg alone cohort data comes out the results should be considerably better than for the combined group. So I think the data so far was encouraging, but the best news is yet to come — and the stock remains a favorite for 2023.
Subscribe to BI Research here…]
tschuss...Yes---Tom Bishop--BI Research----Tom has been a fan of Anavex for quite a long time and has it as one of his top picks for 2023--- https://www.moneyshow.com/expert/cb494a88b95e450b95e7564f10d4a10f/
McM
When will anavex start trying to save human beings from dementia death?
At some point they are willing accomplices to a corrupt and wicked system.
https://finance.yahoo.com/news/anavex-2-73-blarcamesine-receives-113000106.html
Of course, it is not fluff. There is no OLE for the Juvenile Rett trial now so Compassionate Use was needed - and is happening. There is no way to spin this as a bad thing. It is positive. It doesn't mean 2-73 is approved for Rett in Canada, but it is a vote of confidence.
Read it again..."Health Canada's Special Access Program (SAP) for drugs enables drugs that are not marketed in Canada to be requested by practitioners for the treatment, diagnosis, or prevention of serious or life-threatening conditions when conventional therapies have failed, are unsuitable, or are unavailable either as marketed products, or through enrollment in clinical trials. [1]
Christopher U Missling, PhD, President and Chief Executive Officer of Anavex said: “While our clinical studies with ANAVEX®2-73 (blarcamesine) are very critical to collect clinical information for regulatory purposes, we also recognize the long-term commitment to our investigators, patients and families. Therefore, post clinical studies, we are keen to provide supply to the investigators that have requested compassionate use of ANAVEX®2-73 (blarcamesine) for their patients on a global basis. In compliance with local authorities, many patients from our clinical studies are now able to continue treatment with ANAVEX®2-73 (blarcamesine).”
Now we should see just how valuable-critical this long struggle REALLY IS. God bless these KIDS and their long suffering families. There can NOW be a joyful moment of thanks and more work on an effective CNS disease treatment. Thanks to Canada and others WW.
Health Canada's Special Access Program (SAP) for drugs enables drugs that are not marketed in Canada to be requested by practitioners for the treatment, diagnosis, or prevention of serious or life-threatening conditions when conventional therapies have failed, are unsuitable, or are unavailable either as marketed products, or through enrollment in clinical trials. [1]
Christopher U Missling, PhD, President and Chief Executive Officer of Anavex said: “While our clinical studies with ANAVEX®2-73 (blarcamesine) are very critical to collect clinical information for regulatory purposes, we also recognize the long-term commitment to our investigators, patients and families. Therefore, post clinical studies, we are keen to provide supply to the investigators that have requested compassionate use of ANAVEX®2-73 (blarcamesine) for their patients on a global basis. In compliance with local authorities, many patients from our clinical studies are now able to continue treatment with ANAVEX®2-73 (blarcamesine).”
ANAVEX®2-73 Receives Compassionate Use Authorization for Pediatric Patients with Rett Syndrome
https://www.anavex.com/post/anavex-2-73-receives-compassionate-use-authorization-for-pediatric-patients-with-rett-syndrome
Great opportunity to build a larger base of RWD-RWE. Bless the kids and their families.
ANAVEX®2-73 Receives Compassionate Use Authorization for Pediatric Patients with Rett Syndrome
https://www.anavex.com/post/anavex-2-73-receives-compassionate-use-authorization-for-pediatric-patients-with-rett-syndrome
jones325: Agree on observation of an AVXL course correction and would add that (SO FAR) we know of no new vectors or alternate BINGO field assignment. The team obviously has new performance data which validates by observation that they are on the right heading to achieve their goals. Tweaks and fine tuning at pilots discretion, as AI may guide. Bingo destination in sight, contact approach control as planned.
Wonder why Chris Missling didn't exercise his options, I guess he's not concerned since he has a BIG option series coming up in the next few years..
The study reports distribution of scores and other statistical features of the Rett Syndrome Behaviour Questionnaire (RSBQ) in more than 600 children and adults with Rett syndrome. [b[color=red][color=red]]It also re-examines the structure of the questionnaire, specifically the grouping of questions (items) into different subscales. This evaluation led authors to propose some changes to the organization of the questions (i.e., revised subscales). [/color][/color]The study, which represents the largest ever analysis of the RSBQ and the first report of the instrument in adults with Rett Syndrome, was the result of an international collaboration including anonymized databases from the United States, Australia, United Kingdom, and Denmark. The ultimate goal of the project was to provide reference values and other metrics of the RSBQ for its clinical application and implementation in research studies. The study was partially funded by a grant from the International Rett Syndrome Foundation (IRSF). All analyses performed in the study are available to the community through a website hosted by IRSF.
This med/tech publication is also about International LEADERSHIP. The expression, "Herding Cats", comes to mind in the context of ..."Why does this stuff always take so long to do???" (NOW HE TELLS US).
In the EXCELLENCE Phase 2/3 ANAVEX®2-73-RS-003 Rett syndrome pediatric clinical trial, the characterized Rett Syndrome Behavior Questionnaire (RBSQ), together with the Clinical Global Impression Improvement Scale (CGI-I), represent the co-primary efficacy endpoints of the study.
The paper can be accessed online at: https://pubmed.ncbi.nlm.nih.gov/37104862/.
WolfofMia: WOW, clearly an excellent WW collaborative-LEADESRSHIP move by Dr.M. and the RSD team. This is a strong indication of HOW WW CNS Leadership by/through multinational collaboration of clinics and regulatory bodies will happen and is happening. AVXL is , "On the Tip of the Spear". .
https://www.anavex.com/post/anavex-life-sciences-reports-publication-in-medical-journal-for-continued-commitment-to-improve-rsbq
.
jonjones
When we see what’s at stake here, you bet you’re axx that we’re in for a fight. That’s why I was perplexed to hear that Missling was going to the fda first.
Didn’t we want to avoid a corrupt system that may be in the hands of BP? It’s disappointing to hear that we won’t go to the TGA first after all their support.
georgejji Very impressive package, Thx for sharing .
AVXL
https://www.anavex.com/_files/ugd/79bcf7_97da6311c3b643bea8e9a6659bb51422.pdf
Good luck and GOD bless,
crescentmotor...
I am not worried about the FDA sabotaging a compelling AVXL NDA if we get that far.
No argument there. Based on my research, I believe the FDA is largely bought and paid for. No reason to think the FDA stands apart from the other U.S alphabet organizations and I have no faith in any of them.
crescentmotor...
We are well past the rah-rah stage at this point.
HUH????https://finance.yahoo.com/m/1cf2858a-b6ba-3f37-b0fc-aa0e79940252/biogen-takes-alzheimer%E2%80%99s-drug.html
Maybe you can shine SHAT??? Who Knew??
AB-E-NORMAL?
What is ABNORMAL silence a symptom of on AVXL MB?
Never Mind...
AB-E-NORMAL?
What is ABNORMAL silence a symptom of on AVXL MB?
Brain bleeds vs improvement of patients. The game seens rigged for big pharma
falconer
No Useful Information
Classic Piece of FUD... (P.O.F.) IMO